The overall objective is the design and synthesis of site-specific heterobifunctional cleavable protein-DNA and interhelical DNA-DNA crosslinking reagents for use as molecular tools for determining the teritary structure of biologically important macromolecules. We will use these reagents in collaboration with molecular biologists as in vitro and in vivo probes for the study of protein-nucleic acid complexes and packaged nucleic acid in viruses and condensed chromatin.